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Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement

Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through th...

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Main Authors: Schröder-Braunstein, Jutta (Author) , Pavlov, Vladimir (Author) , Giese, Thomas (Author) , Heidtmann, Antje (Author) , Wentrup, Sabine (Author) , Lasitschka, Felix (Author) , Ulrich, Alexis (Author) , Engelke, Antonia (Author) , Saeedi, Mohammed al (Author) , Meuer, Stefan (Author)
Format: Article (Journal)
Language:English
Published: 2012
In: Clinical & experimental immunology
Year: 2011, Volume: 168, Issue: 1, Pages: 87-94
ISSN:1365-2249
DOI:10.1111/j.1365-2249.2011.04539.x
Online Access:Verlag, Volltext: http://dx.doi.org/10.1111/j.1365-2249.2011.04539.x
Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390499/
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Author Notes:J. Schröder-Braunstein, V. Pavlov, T. Giese, A. Heidtmann, S. Wentrup, F. Lasitschka, J. Winter, A. Ulrich, A. Engelke, M. Al Saeedi and S. Meuer
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Summary:Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through the ‘co-stimulatory’ CD2-receptor is enhanced when compared to PBT. In this study, we demonstrate that engagement of another co-stimulatory receptor on both LPT and PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly activates the former but not the latter through a PI3-kinase dependent signalling pathway leading to the production of inflammatory cytokines such as interleukin (IL)-2, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition to the high sensitivity of LPT to CD2 stimulation, this finding supports the notion that ‘non-specific/innate’ mechanisms to activate T lymphocytes play a predominant role vis-à-vis‘TCR driven/adaptive’ responses in the intestinal mucosa. Furthermore, it suggests that results from preclinical tests for therapeutic antibodies performed with human blood derived T cells are probably insufficient to predict reactivities of tissue-resident immune cells, which - given their quantitative predominance - may critically determine the in-vivo response to such compounds.
Item Description:Published online: 28 November 2011
Gesehen am 11.04.2018
Physical Description:Online Resource
ISSN:1365-2249
DOI:10.1111/j.1365-2249.2011.04539.x

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